At Virginia Tech Wallace began as Professor of Biology (1981-83), then became the Biology Department's second University Distinguished Professor (1983-94). He published >15 books and >100 research papers mostly before his arrival at Virginia Tech, especially using, Drosophila as a genetic model. A recipient of numerous honors and awards during his career, Wallace's appointment to the National Academy of Sciences in 1970 illustrates his eminence. Throughout his career, but especially during the later years, ecology and environmental science gained his interest. This led to the popular, university-wide World Watch Seminar series and several books. Wallace retired in 1994.

At his residence in Blacksburg, Wallace continues to write books and papers.